Novel bioreactor design for the culture of suspended mammalian cells. Part I: Mixing characterization

Cervantes, María Irene Sánchez; Lacombe, Justin; Muzzio, Fernando J.; Álvarez, Mario Moisés

doi:10.1016/j.ces.2006.09.035

Cited by 25 publications

(23 citation statements)

References 43 publications

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“…Indeed, open impellers generate segregated regions in the laminar regime irrespective of the discharge flow type, whether radial or axial (see Figure 1). Recent studies on open impellers (Alvarez, 2000;Ascanio et al, 2002a,b;Alvarez et al, 2002;Hall et al, 2005a;Sanchez Cervantes et al, 2006) conclude that, in the laminar regime, the dynamic perturbations generated by using an eccentric shaft could help to break up the segregated regions, and increase the axial circulation in a tank even with radial agitator. This change in flow patterns prevents the formation of flow compartmentalization and helps to improve the mixing efficiency of the mixing device.…”

Section: Introductionmentioning

confidence: 97%

Effect of shaft eccentricity on the laminar mixing performance of a radial impeller

2008

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The effects of impeller eccentricity and Reynolds number on the mixing performance were studied for Rushton turbine stirred tank systems operated in the laminar regime (Re < 10). A digital image analysis of an acid-base decolourization reaction was used to characterize the mixing efficiency. Results show that both parameters have remarkable effects on the destruction of the toroidal segregated regions surrounding the Rushton turbine in laminar flow. Criteria are given to prevent the formation of these segregated regions in a tank. It is also shown that shaft eccentricity does not impact on the impeller power consumption.Les effets de l'excentrage du mobile d'agitation et du nombre de Reynolds sur les performances d'une turbine Rushton opérée en régime laminaire (Re < 10) ontétéétudiés. Une analyse d'images numériques issues d'une réaction de décoloration acide-base aété utilisée pour caractériser l'efficacité du mélange. Les résultats montrent que ces deux paramètres ont des effets remarquables sur la destruction des zones toroïdales non mélangées entourant la turbine Rushton en régime laminaire. Des critères ont ainsiétéétablis afin d'éviter la formation de ces zones ségrégées dans une cuve. De plus, il aété montré que l'excentrage de l'arbre n'a pas d'impact sur la consommation de puissance de l'agitateur.

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Section: Introductionmentioning

confidence: 97%

Effect of shaft eccentricity on the laminar mixing performance of a radial impeller

2008

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“…For instance, the torus-shaped, segregated regions observed with the turbine impeller in laminar flow can be eliminated when using time-dependent impeller rotational speed [7,[13][14][15] or off-center impellers [12,[16][17][18][19][20]. Another idea, suggested by Alvarez et al [21,22], consists of creating the "disorder" directly from the impeller.…”

Section: Introductionmentioning

confidence: 99%

New Turbine Impellers for Viscous Mixing

Cabaret¹,

Fradette²,

Tanguy³

2008

Chem Eng & Technol

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New open impellers developed for viscous mixing applications were characterized experimentally in terms of power consumption and mixing times, and their performance was compared to that of standard turbines. Their design is based on a nonsymmetry of revolution principle contrary to standard impellers. A color-discoloration technique based on a fast acid-base indicator reaction and image analysis were used to evaluate the mixing efficiency. Experimental results show that the segregated, torus-shaped regions, always observed above and below standard turbine impellers, can be significantly reduced using the new turbine designs generating a well-balanced axial-radial flow field.

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“…Three geometrical features are crucial in the design of this mixing vessel: (a) the eccentricity of the impeller shaft, (b) the round bottom, and (c) the use of an angled‐disc impeller. From these three elements, eccentricity is a determinant in defining a chaotic flow field (Alvarez, 2000; Alvarez et al, 2002a; Sánchez‐Cervantes et al, 2006). Chaos is promoted by breaking time or space symmetries (Alvarez et al, 2002b; Alvarez‐Hernández et al, 2002; Hobbs et al, 1997; Lamberto et al, 2001).…”

Section: Resultsmentioning

confidence: 99%

“…Chaos is promoted by breaking time or space symmetries (Alvarez et al, 2002b; Alvarez‐Hernández et al, 2002; Hobbs et al, 1997; Lamberto et al, 2001). A simple and effective way to disrupt flow symmetry in a stirred tank is by displacing the agitation shaft to an eccentric position (Alvarez et al, 2002a; Sánchez‐Cervantes et al, 2006). However, in eccentric stirred tanks with flat bottom, segregated or low‐rate mixing regions can be observed at the lower corners of the tank (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In stirred tanks commonly used in industry and lab applications, the agitation axis is centrally located (concentric). However, the use of eccentrically agitated systems as mixing vessels has recently received research attention (Alvarez et al, 2002a; Ascanio et al, 2002; Cabaret et al, 2008; Galleti and Brunazzi, 2008; Hu et al, 2010; Karcz et al, 2005; Lai and Yang, 2010; Montante et al, 2006; Sánchez‐Cervantes et al, 2006; Szoplik and Karcz, 2008; Takahashi et al, 2011; Yang et al, 2008, 2011; Woziwodzki and Jedrzejczak, 2010), although it has not been documented in the context of biotechnology applications.…”

Section: Introductionmentioning

confidence: 99%

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A simple eccentric stirred tank mini‐bioreactor: Mixing characterization and mammalian cell culture experiments

Bulnes-Abundis

Carrillo-Cocom

Araíz-Hernández

et al. 2012

Biotech & Bioengineering

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In industrial practice, stirred tank bioreactors are the most common mammalian cell culture platform. However, research and screening protocols at the laboratory scale (i.e., 5-100 mL) rely primarily on Petri dishes, culture bottles, or Erlenmeyer flasks. There is a clear need for simple-easy to assemble, easy to use, easy to clean-cell culture mini-bioreactors for lab-scale and/or screening applications. Here, we study the mixing performance and culture adequacy of a 30 mL eccentric stirred tank mini-bioreactor. A detailed mixing characterization of the proposed bioreactor is presented. Laser induced fluorescence (LIF) experiments and computational fluid dynamics (CFD) computations are used to identify the operational conditions required for adequate mixing. Mammalian cell culture experiments were conducted with two different cell models. The specific growth rate and the maximum cell density of Chinese hamster ovary (CHO) cell cultures grown in the mini-bioreactor were comparable to those observed for 6-well culture plates, Erlenmeyer flasks, and 1 L fully instrumented bioreactors. Human hematopoietic stem cells were successfully expanded tenfold in suspension conditions using the eccentric mini-bioreactor system. Our results demonstrate good mixing performance and suggest the practicality and adequacy of the proposed mini-bioreactor.

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Novel bioreactor design for the culture of suspended mammalian cells. Part I: Mixing characterization

Cited by 25 publications

References 43 publications

Effect of shaft eccentricity on the laminar mixing performance of a radial impeller

Effect of shaft eccentricity on the laminar mixing performance of a radial impeller

New Turbine Impellers for Viscous Mixing

A simple eccentric stirred tank mini‐bioreactor: Mixing characterization and mammalian cell culture experiments

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